Amelioration of hypertriglyceridemia with hypo-alpha-cholesterolemia in LPL deficient mice by hematopoietic cell-derived LPL

Yinyuan Ding, Ling Zhang, Yuhui Wang, Wei Huang, Yin Tang, Lu Bai, Colin J.D. Ross, Michael R. Hayden, George Liu

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Macrophage-derived lipoprotein lipase (LPL) has been shown uniformly to promote atherosclerotic lesion formation while the extent to which it affects plasma lipid and lipoprotein levels varies in wild-type and hypercholesterolemic mice. It is known that high levels of LPL in the bulk of adipose tissue and skeletal muscle would certainly mask the contribution of macrophage LPL to metabolism of plasma lipoprotein. Therefore, we chose LPL deficient (LPL -/-) mice with severe hypertriglyceridemia as an alternative model to assess the role of macrophage LPL in plasma lipoprotein metabolism via bone marrow transplant, through which LPL will be produced mainly by hematopoietic cell-derived macrophages. Methods and Results: Hypertriglyceridemic LPL -/- mice were lethally irradiated, then transplanted with bone marrow from wild-type (LPL +/+) or LPL -/- mice, respectively. Sixteen weeks later, LPL +/+ →LPL -/- mice displayed significant reduction in plasma levels of triglyceride and cholesterol (408±44.9 vs. 2.7±0.5×10 3 and 82.9±7.1 vs. 229.1±30.6 mg/dl, p<0.05, respectively), while a 2.7-fold increase in plasma high density lipoprotein- cholesterol (p<0.01) was observed, compared with LPL -/-→LPL -/- control mice. The clearance rate for the oral fat load test in LPL +/+ →LPL -/- mice was faster than that in LPL -/-→LPL -/- mice, but slower than that in wild-type mice. Liver triglyceride content in LPL +/+→LPL -/- mice was also significantly increased, compared with LPL -/-→LPL -/- mice (6.8±0.7 vs. 4.6±0.5 mg/g wet tissue, p<0.05, n = 6). However, no significant change was observed in the expression levels of genes involved in hepatic lipid metabolism between the two groups. Conclusions: Hematopoietic cell-derived LPL could efficiently ameliorate severe hypertriglyceridemia and hypo-alpha-cholesterolemia at the compensation of increased triglyceride content of liver in LPL -/- mice.

Original languageEnglish (US)
Article numbere25620
JournalPLoS One
Volume6
Issue number9
DOIs
StatePublished - Sep 29 2011

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hypertriglyceridemia
lipoprotein lipase
Lipoprotein Lipase
Hypertriglyceridemia
mice
cells
Macrophages
Plasmas
macrophages
lipoproteins
Lipoproteins
Triglycerides
triacylglycerols
Metabolism
Liver
liver
Bone
Bone Marrow

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Amelioration of hypertriglyceridemia with hypo-alpha-cholesterolemia in LPL deficient mice by hematopoietic cell-derived LPL. / Ding, Yinyuan; Zhang, Ling; Wang, Yuhui; Huang, Wei; Tang, Yin; Bai, Lu; Ross, Colin J.D.; Hayden, Michael R.; Liu, George.

In: PLoS One, Vol. 6, No. 9, e25620, 29.09.2011.

Research output: Contribution to journalArticle

Ding, Yinyuan ; Zhang, Ling ; Wang, Yuhui ; Huang, Wei ; Tang, Yin ; Bai, Lu ; Ross, Colin J.D. ; Hayden, Michael R. ; Liu, George. / Amelioration of hypertriglyceridemia with hypo-alpha-cholesterolemia in LPL deficient mice by hematopoietic cell-derived LPL. In: PLoS One. 2011 ; Vol. 6, No. 9.
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abstract = "Background: Macrophage-derived lipoprotein lipase (LPL) has been shown uniformly to promote atherosclerotic lesion formation while the extent to which it affects plasma lipid and lipoprotein levels varies in wild-type and hypercholesterolemic mice. It is known that high levels of LPL in the bulk of adipose tissue and skeletal muscle would certainly mask the contribution of macrophage LPL to metabolism of plasma lipoprotein. Therefore, we chose LPL deficient (LPL -/-) mice with severe hypertriglyceridemia as an alternative model to assess the role of macrophage LPL in plasma lipoprotein metabolism via bone marrow transplant, through which LPL will be produced mainly by hematopoietic cell-derived macrophages. Methods and Results: Hypertriglyceridemic LPL -/- mice were lethally irradiated, then transplanted with bone marrow from wild-type (LPL +/+) or LPL -/- mice, respectively. Sixteen weeks later, LPL +/+ →LPL -/- mice displayed significant reduction in plasma levels of triglyceride and cholesterol (408±44.9 vs. 2.7±0.5×10 3 and 82.9±7.1 vs. 229.1±30.6 mg/dl, p<0.05, respectively), while a 2.7-fold increase in plasma high density lipoprotein- cholesterol (p<0.01) was observed, compared with LPL -/-→LPL -/- control mice. The clearance rate for the oral fat load test in LPL +/+ →LPL -/- mice was faster than that in LPL -/-→LPL -/- mice, but slower than that in wild-type mice. Liver triglyceride content in LPL +/+→LPL -/- mice was also significantly increased, compared with LPL -/-→LPL -/- mice (6.8±0.7 vs. 4.6±0.5 mg/g wet tissue, p<0.05, n = 6). However, no significant change was observed in the expression levels of genes involved in hepatic lipid metabolism between the two groups. Conclusions: Hematopoietic cell-derived LPL could efficiently ameliorate severe hypertriglyceridemia and hypo-alpha-cholesterolemia at the compensation of increased triglyceride content of liver in LPL -/- mice.",
author = "Yinyuan Ding and Ling Zhang and Yuhui Wang and Wei Huang and Yin Tang and Lu Bai and Ross, {Colin J.D.} and Hayden, {Michael R.} and George Liu",
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AU - Ding, Yinyuan

AU - Zhang, Ling

AU - Wang, Yuhui

AU - Huang, Wei

AU - Tang, Yin

AU - Bai, Lu

AU - Ross, Colin J.D.

AU - Hayden, Michael R.

AU - Liu, George

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Y1 - 2011/9/29

N2 - Background: Macrophage-derived lipoprotein lipase (LPL) has been shown uniformly to promote atherosclerotic lesion formation while the extent to which it affects plasma lipid and lipoprotein levels varies in wild-type and hypercholesterolemic mice. It is known that high levels of LPL in the bulk of adipose tissue and skeletal muscle would certainly mask the contribution of macrophage LPL to metabolism of plasma lipoprotein. Therefore, we chose LPL deficient (LPL -/-) mice with severe hypertriglyceridemia as an alternative model to assess the role of macrophage LPL in plasma lipoprotein metabolism via bone marrow transplant, through which LPL will be produced mainly by hematopoietic cell-derived macrophages. Methods and Results: Hypertriglyceridemic LPL -/- mice were lethally irradiated, then transplanted with bone marrow from wild-type (LPL +/+) or LPL -/- mice, respectively. Sixteen weeks later, LPL +/+ →LPL -/- mice displayed significant reduction in plasma levels of triglyceride and cholesterol (408±44.9 vs. 2.7±0.5×10 3 and 82.9±7.1 vs. 229.1±30.6 mg/dl, p<0.05, respectively), while a 2.7-fold increase in plasma high density lipoprotein- cholesterol (p<0.01) was observed, compared with LPL -/-→LPL -/- control mice. The clearance rate for the oral fat load test in LPL +/+ →LPL -/- mice was faster than that in LPL -/-→LPL -/- mice, but slower than that in wild-type mice. Liver triglyceride content in LPL +/+→LPL -/- mice was also significantly increased, compared with LPL -/-→LPL -/- mice (6.8±0.7 vs. 4.6±0.5 mg/g wet tissue, p<0.05, n = 6). However, no significant change was observed in the expression levels of genes involved in hepatic lipid metabolism between the two groups. Conclusions: Hematopoietic cell-derived LPL could efficiently ameliorate severe hypertriglyceridemia and hypo-alpha-cholesterolemia at the compensation of increased triglyceride content of liver in LPL -/- mice.

AB - Background: Macrophage-derived lipoprotein lipase (LPL) has been shown uniformly to promote atherosclerotic lesion formation while the extent to which it affects plasma lipid and lipoprotein levels varies in wild-type and hypercholesterolemic mice. It is known that high levels of LPL in the bulk of adipose tissue and skeletal muscle would certainly mask the contribution of macrophage LPL to metabolism of plasma lipoprotein. Therefore, we chose LPL deficient (LPL -/-) mice with severe hypertriglyceridemia as an alternative model to assess the role of macrophage LPL in plasma lipoprotein metabolism via bone marrow transplant, through which LPL will be produced mainly by hematopoietic cell-derived macrophages. Methods and Results: Hypertriglyceridemic LPL -/- mice were lethally irradiated, then transplanted with bone marrow from wild-type (LPL +/+) or LPL -/- mice, respectively. Sixteen weeks later, LPL +/+ →LPL -/- mice displayed significant reduction in plasma levels of triglyceride and cholesterol (408±44.9 vs. 2.7±0.5×10 3 and 82.9±7.1 vs. 229.1±30.6 mg/dl, p<0.05, respectively), while a 2.7-fold increase in plasma high density lipoprotein- cholesterol (p<0.01) was observed, compared with LPL -/-→LPL -/- control mice. The clearance rate for the oral fat load test in LPL +/+ →LPL -/- mice was faster than that in LPL -/-→LPL -/- mice, but slower than that in wild-type mice. Liver triglyceride content in LPL +/+→LPL -/- mice was also significantly increased, compared with LPL -/-→LPL -/- mice (6.8±0.7 vs. 4.6±0.5 mg/g wet tissue, p<0.05, n = 6). However, no significant change was observed in the expression levels of genes involved in hepatic lipid metabolism between the two groups. Conclusions: Hematopoietic cell-derived LPL could efficiently ameliorate severe hypertriglyceridemia and hypo-alpha-cholesterolemia at the compensation of increased triglyceride content of liver in LPL -/- mice.

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